CENTRAL NERVOUS

SYSTEM MALFORMATIONS
Oana Tarta-Arsene

DEPARMENT OF PEDIATRIC NEUROLOGY

PSYCHIATRY CLINICAL HOSPITAL AL. OBREGIA

Definition
Morphologic anomalies secondary to:
Stopping in development or
Abnormal development
Central nervous structures before birth;
Various clinical syndromes;
Different causes:
Environmental causes (80%)
Physical agents: traumatisms, X-rays radiations etc;
Infectious agents: TORCH;
Metabolic agents: phenilcetonuria, mellitus diabetes etc;
Toxic: CO, ethylic alcohol etc;
Intrinsic factors (20%): genetic factors;
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Normal development of CNS

1. DORSAL INDUCTION:
Neural plate (thickening of
the ectoderm under
induction of the notochord)
neural groove neural
crest closed (Neural
tube) 4 wk
Anterior 24-26 day;
Posterior 26-29 day;

NORMAL DEVELOPMENT OF THE CNS

2. VENTRAL INDUCTION (30-90 days)
3 vesicles:
Prosencephalon
telencephalic vesicles cerebral hemispheres;
diencephalon;

Mezencephalon midbrain;
Rombencephalon
metencephalon (pons & cerebellum)
mielencephalon (medulla)

NORMAL DEVELOPMENT OF THE CNS

3. NEURONAL AND GLIAL
PROLIFERATION:
birth;

ABNORMAL DEVELOPMENT OF THE CNS

1. DORSAL INDUCTION ( 4 wk)
Disorders of the neurulation ANENCEPHALY;
Disorders of the closing of the neural tube DYSRAPHISM;
Disorders of the developing of the cervical somites ARNOLDCHIARI SDR.;
2. VENTRAL INDUCTION ( 12 wk)
Disorders of segmentation and cleavage
HOLOPROSENCEPHALY;
3. CORTICAL DEVELOPMENT ( birth)
Disorders of neuronal migration and cortex structure
LISSENCEPHALY, POLYMICROGYRIA, NEURONAL
HETEROTOPY, CORTICAL DYSPLASIA;

DISORDERS OF THE DORSAL

INDUCTION
ANENCEPHALY
Lethal condition characterized by
absence of both cerebral hemisphere
and skull;
Clinical data:
New-born only with visceroskull
(face eyes);
Survive days 2 wks;
Some stereotypic movements,
spontaneously, few archaic
reflexes (Moro);
Diagnosis:
antenatal: ecography + levels of
alpha-fetoprotein + amniocentesis;
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DISORDERS OF THE DORSAL

INDUCTION
DYSRAPHISM:

Imperfect formation of the midline mesenchymal, bony and

neural structures secondary to imperfect closing the neural
tube;

Classification:
1. Type of structure herniated:
1. Meanings: meningocele;
2. Nervous tissue + meninges:
encephalocele/myelomeningocele;
2.

Localization:
1. Cranial: encephalocele/ meningocele;
2. Spinal: spina bifida cystica / occulta;
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DISORDERS OF THE DORSAL

INDUCTION
CRANIAL: herniation of the nervous tissues +/- meninges
outside the skull;
Classification (type of tissue):
Cranial meingocele: covered / not by abnormal skin (hemangioma
etc);
Encephalocele (associate frequent with hydrocephaly):
Post (85%): supra / infratenthorial;
Ant (15%): sphenoid / ethmoidal etc;

Para clinical diagnosis:

Rx, CT, MRI;
Alpha-fetoprotein (mother + amniotic liquid);

Clinical signs (depending of the herniated tissue):

pyramidal s, mental retardation, epilepsy, visual deficiencies etc;
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DISORDERS OF THE DORSAL

INDUCTION
1.

SPINAL
SPINA BIFIDA CYSTICA (herniation of the nervous tissue)
Meningocele;
Localization: thoraco-lombar/lombo-sacral;
Clinical data: frequent no signs, high risk of infection;
Myelomenigocele (95%):
Localization: lombo-sacral / rare cervical;
Clinical data:
Frequent uncovered by skin, only abnormal meninges;
Motor signs:
Lower unit motor s. (peripheral nerve impairment);
Upper unit motor s. (spinal cord impairment);
Sphincter disturbances;
Sensitive s.;
Hydrocephalus;
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DISORDERS OF THE DORSAL

INDUCTION
1.

SPINA BIFIDA CYSTICA (herniation of the nervous

tissue)
Diagnosis:
Imagistic : ecography, Rx, CT, IRM;
alpha-fetoprotein;

Treat: surgical, < 3 mo;

Prevention:
folic acid 1 mo before + 2 mo of pregnancy;

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DISORDERS OF THE DORSAL

INDUCTION
2.

SPINA BIFIDA OCCULTA:

Def: no herniation of the nervous tissue but:
More vertebras affected;
Neurological signs secondary to medullar impairment;
DD: simple osseous defect at 10% of children, asymptomatic;
Diagnosis:
Skin signs:
nevus, dermal sinuses, deviation of the interfesier fold skin, hair zone,
hemangioma etc;

Neurological s.: no / mild / severe, progressive;

Asymptomatic progressive symptomatic secondary to the growing
of the spinal cord;

Orthopedic + sphincter s;
Imagistic s.: Rx / CT / MRI;
Treat: surgical;
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DISORDERS OF THE DORSAL

INDUCTION
2.

SPINA BIFIDA OCCULTA:

Types:
1.

SHORT FILUM TERMINALE:

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DISORDERS OF THE DORSAL

INDUCTION
2. SPINAL LIPOMAS (most frequent):

Collection of fat and connective tissue partially

encapsulated and associated with failure of fusion of thee
posterior bony structures;
Spinal cord is fixed to the meninges and skin;

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DISORDERS OF THE DORSAL

INDUCTION
3. DORSAL DERMAL SINUSES:

Epithelium-lined dermal tubes that courses from the skin

surfaces toward CNS;
Complication: INFECTIOUS (recurrent meningitis +
hydrocephalus);

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DISORDERS OF THE DORSAL

INDUCTION
4. DIASTEMATOMYELIA:
Sagittal cleft dividing the spinal cord into 2 half-cords
each surrounded by its own pia matter;

5. DIPLOMYELIA:

Double of the spinal cord up to 10 segments, frequent

asymptomatic;

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ABNORMALITIES OF THE DEVELOPMENT OF

THE CERVICAL SOMITES
ARNOLD-CHIARI sdr.:
Abnormal position of the junction between medulla and spinal
cord and also cerebellum in rapport to the foramen magnum;
Types:
Type I: caudal displacement of the lower poles of cerebellum
hemispheres up to C3;

symptomatic in adolescence;
Recurrent headache, stiff neck;
Impairment of cranial nv (medulla) +Cerebellar s. + signs of
spinal cord compression;

Type II: caudal displacement of the medulla and the lower part
of the pons along with the cerebellar hemispheres;

Symptomatic: early;
Associated with hydrocephalus & myelomeningocele;
Cerebellar s. + cranial nv s. + s. of spinal cord compression;

Type III, IV;

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Disorders of segmentation and

cleavage
HOLOPROZENCEPHALY (abnormal cleavage of the telencephalon in 5-6
wk)
there are 3 types anatomical-pathological :
Alobar form: total absence of cleavage;
single cerebral hemisphere, single ventricle, absence interemispheric
interemispheric bonds
(corpus calosus), single optical nv;

Semilobar form:
failure of cleavage in anterior part of telencephalon;
single ventricle in the horseshoe, without body corpus calosus;

Lobar form:
Anterior defect in cleavage of cerebral hemispheres;
2 cerebral hemispheres + neocortex frontal anterior merged + the rest normal;

Etiology: genetically transmit (more syndromes..)

Clinical data: dysmorphism (gigantic, cebocephaly) +
Endocrine, neurological, mental s.

Diagnosis: MRI;
Prognosis poor;
Treatment symptomatic;
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Disorders of neuronal migration

and cortex structure
MICROCEPHALY:
Decrease in the volume and
weight of the brain manifested
by cranial perimeter less than
2 standard deviations
compared to the average of
age, sex and race;

MACROCEPHALY:
Increase volume and brain
weight manifested by a
greater cranial perimeter with
more than 2 standard
deviations compared to
average of age, sex and race;

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Normal cranial perimeters growing

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Disorders of neuronal migration

and cortex structure
LISENCEPHALY (smooth brain);
POLYMYCROGYRIA: neurons reach the cortex but distribute
abnormally, smaller gyrus and larger number;

NEURONAL HETEROTOPHY: neurons with normal structure, but

abnormal location and impaired synaptic connections ;

CORTICAL DYSPLAZIA: focal abnormality of the cerebral cortex;

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LYSENCEPHALY

(smooth brain);

2 principals types:
Type I predominantly anterior (LYSI gene)
Type II predominantly posterior (DCX gene X- linkage)
+ other genes...
diagnosis antenatal / postnatal (cerebral MRI)
clinical signs: epilepsy, mental + motor retardation;
Prognosis poor;
! GENETICAL ADVICE!!
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POLYMYCROGYRIA:
neurons reach the cortex but distribute abnormally, smaller gyrus and larger
number

EPILEPSY, SPASTICITY,
MENTAL RETARDATION

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NEURONAL HETEROTOPY
(neurons with normal structure, but abnormal location and impaired
synaptic connections)

EPILEPSY, MENTAL
RETARDATION, NEUROLOGICAL
S.

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CORTICAL DYSPLASIA
(focal abnormality of the cerebral cortex)

EPILEPSY RESISTANT TO
TREATMENT

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CRANIOSTENOSIS
DEFINITION: premature closure of one or more cranial
sutures in front of a developing brain, having the
consequence of skull deformation compensation;
Virchow's law:
the bone growth is inhibited in the perpendicular direction, with
increasing compensatory parallel with closed suture!!!;

Etiology:
Primary: anomaly of the mesenchymal matrix;
Secondary to mechanical disorders (shunted hydrocephalus),
metabolic (vitamin-resistant rickets) etc.;

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CRANIOSTENOSIS
NORMAL SUTURES:

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CRANIOSTENOSIS
Metopic sutures stenosis TRIGONOCEPHALY:

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CRANIOSTENOSIS
Coronal sutures stenosis:
Unilateral PLAGIOCEPHALY
Bilateral BRAHICEPHALY (reduced ant-post diameter, increased
transverse diameter)

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CRANIOSTENOSIS
Sagital sutures stenosis SCAFOCEPHALY (increased ant-post
diameter, decreased transverse diameter);

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CRANIOSTENOSIS
Lambdoid sutures stenosis:
Unilateral PLAGYOCEPHALY
Bilateral PAHICEPHALY (flat occipital)

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CRANIOSTENOSIS
Stenosis of the coronal sutures coronal + lambdoid + sagital
OXICEPHALY (skull very high )

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CRANIOSTENOSIS
Clinical data:
1. Dysmorphism;
2. Ophthalmologic signs:
1. Mechanical disturbances: exophthalmia, hypertelorism,
strabismus;
2. Visual disturbances: modification of the ocular funds
(papillary edema) etc;
3. Neuro-mental signs:
Hydrocephaly;
Epilepsy;
Mental retardation;
4. Endocrinological signs:
Retard in somatic development;
Adipose-genital syndrome;
Insipid us diabetes;
Mix edema;
Treat: neurosurgical craniotomy in the first 3-6 mo of life;
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TAKE HOME MESSAGES!

1.
2.
3.

There are more cerebral and spinal malformations and

all are dependent on the time of insults;
Most of them have genetically predisposition
genetically advice!
Clinical signs: depending on the tissue affected:
+ skin signs (dorsal induction abnormalities);
+ upper motor unit signs (spinal cord cerebral abnormalities)
+ lower motor unit signs (spinal dysraphism);
+ mental retardation (cerebral abnormalities);
+ epilepsy (gray matter involvement);

4.

Diagnosis:
Imagistic exams (antenatal !! + postnatal);
Alpha-fetoprotein incomplete closure of the neural tube;

5.

Treatment:
Symptomatic;
+/- Neurosurgery;

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